Lecture 15 Pain Syndromes and Analgesics

Question 1

Pain

Answer 1

A normal unpleasant physical sensation associated with tissue damage or dysfunction

Question 2

What are the two major types of pain?

Answer 2

Physiological (nociceptive) and chronic (intractable, neuropathic)

Question 3

Congentical absence of pain…

Answer 3

Rare genetic defect in which a person has normal skin sensation but is unable to perceive pain from birth; compound fractures, loss of body parts can go unnoticed

Question 4

Nociception

Answer 4

“noxious perception” the perception of pain

Question 5

Nociceptor

Answer 5

Receptor for stimuli (chemical, mechanical, thermal) that result in pain perception; located on free nerve endings in skin, muscle, organs

Question 6

Analgesia

Answer 6

absence of pain

Question 7

Anesthesia

Answer 7

Absence of all sensory perception

Question 8

Anesthetic

Answer 8

A substance that reduces perception of numerous senses (touch, pain, temperature, pressure)

Question 9

Analgesic

Answer 9

A substance that diminishes the perception of pain

Question 10

Names some pain syndromes

Answer 10

Lower back pain
Headache /migraine
Cancer-related
Fibromyalgia
Sciatica
Diabetic neuropathy
Shingles
Phantom limb pain
burn pain
Arthritis
Trigeminal neuroalgia

Question 11

A(delta) fibers

Answer 11

Myelinated fibers (20 m/sec) for quick, sharp pain

Question 12

C fibers

Answer 12

Unmyelinated fibers (2 m/sec) for dull, slow pain

Question 13

Aβ fibers

Answer 13

normal mechanical stimuli signals

Question 14

PN

Answer 14

Projection neurons (ascends up to brain); receive pain signals at the dorsal root of the spinal cord

Question 15

What are the nerve fibers that conduct pain signals?

Answer 15

A(delta), C fibers, Projection neurons

Question 16

What results from tissue damage?

Answer 16

Tissue damage causes the release of various chemicals that activate pain fibers, such as histamine, bradykinin (BK), and prostaglandins.

Question 17

TRP receptors

Answer 17

Transient receptor potential (TRP) receptors, including vanilloid receptors (i.e., VR1) are thermosensitive and chemosensitive receptors on free nerve endings.

Question 18

What activates TRP receptors

Answer 18

Activated by heat, changes in pH, capsaicin (chili peppers), wasabi, etc

Question 19

How does pain arise from demyelination?

Answer 19

Accumulation of voltage-sensitive sodium channels (VSSCs) in demyelinated areas of sensory neurons increases ectopic (“out of place”, spontaneous) activity, and hypersensitivity to normal sensations

Question 20

How does pain occur after severing a nerve?

Answer 20

Neuroma – misguided bundle of newly sprouted nerve fibers following nerve cut

Accumulation of VSSCs in neuromas increases ectopic activity, and hypersensitivity to normal sensations

Question 21

Neuroma

Answer 21

Misguided bundle of newly sprouted nerve fibers following nerve cut.

Question 22

Where does all sensory information enter in the spinal cord?

Answer 22

The dorsal horn of the spinal cord.

Question 23

Where is the reduction of emotional components of pain managed?

Answer 23

The amygdala

Question 24

Where does the inhibition of pain signals occur

Answer 24

The thalamus

Question 25

Spinal and supraspinal analgesia

Answer 25

spinal analgesia is when drugs act at the spine supraspinal is when drugs act at the brain

Question 26

What are the pain neurotransmitters in the spinal cord?

Answer 26

opioid (µ, delta, kappa), 5-HT, and NE

Question 27

What modulates descending pain pathways?

Answer 27

NE (from locus coeruleus) and 5-HT (from raphe nuclei) modulate pain in the spinal cord SSRI, SNRI, NRIs can thus alleviate chronic pain in some patients

Question 28

Name some local anesthetics?

Answer 28

Novocaine, lidocaine, cocaine

Question 29

How do local anesthetics work?

Answer 29

- block VSSCs on sensory neurons - loss of action potentials results in reduced sensation of pain, touch, pressure, temperature (numbness) - must be given locally (i.e., topical subcutaneous injection, epidural)

Question 30

COX

Answer 30

Cyclooxygenase (COX) - enzyme that produces prostaglandins which are released from cells after tissue injury; prostaglandins activate pain pathways

Question 31

NSAID

Answer 31

- Non-steroidal anti-inflammatory drugs (NSAIDs) are COX inhibitors - aspirin, ibuprofen, naproxen, acetaminophen (Tylenol), prescription COX inhibitors (Vioxx, Celebrex)

Question 32

Synthetic steroids

Answer 32

(i.e. hydrocortisone, prednisone) – reduce peripheral inflammation (not via COX inhibition), but long term use is harmful to immune system

Question 33

Anticonvulsants can be used for what type of pain?

Answer 33

Neuropathic pain

Question 34

What are the mechanisms of anticonvulsants for pain?

Answer 34

- Inhibition of VSSCs and voltage-sensitive Ca+ channels | - Inhibition of GABA reuptake/metabolism

Question 35

Where do opiates act on?

Answer 35

Act primarily on mu (m) opioid receptors located on primary afferent terminals in dorsal horn of spinal cord.

Question 36

What normally activates the mu opioid receptors?

Answer 36

normally activated by endorphins and enkephalins inhibit transmission of pain signals to brain

Question 37

What are some side effects of opioids?

Answer 37

side effects include sedation, respiratory depression, constipation, tolerance, dependence, & addiction.

Question 38

What are endocannabinoids generated from?

Answer 38

Arachidonic acid (a fatty acid found in the cell membrane) after stimulation of certain neurotransmitter receptors.

Question 39

Cannabinoids are what type of messenger?

Answer 39

Act as retrograde messengers to inhibit neurotransmitter release.

Question 40

THC is an agonist at what receptors?

Answer 40

THC is an agonist at cannabinoid (CB1) receptors

Question 41

What are 3 synthetic THC and cannabinoids?

Answer 41

Sativex, Marinol, Cesamet

Question 42

Why can't cannabinoids be stored in vesicles?

Answer 42

They are highly lipid soluble (therefore cannot be stored in vesicles)

Question 43

What are the 4 phases of a migraine?

Answer 43

- Prodrome - Aura - Pain phase - Postdrome

Question 44

Prodrome

Answer 44

Symptoms such as altered mood, fatigue, yawning, excessive sleepiness, craving for certain food, stiff muscles, hot ears, GI problems, etc. appear hours to days before migraine

Question 45

Aura

Answer 45

Disturbance of vision just before headache

Question 46

Pain phase

Answer 46

Headache on one side of head with nausea, photophobia

Question 47

Postdrome

Answer 47

Exhaustion, irritability, depression

Question 48

What are common migraine triggers?

Answer 48

- Estrogen and progesterone - Alcohol, chocolate, etc. - Stress, physical activity - Sight, smells - Certain medications

Question 49

What are four types of headaches?

Answer 49

Sinus, cluster, tension, migraine

Question 50

Trepenation

Answer 50

Medieval treatment | (drilling hole in skull), hot iron to the head, blood letting.

Question 51

What was the first effective medication for migraines?

Answer 51

Ergotamine which constricts blood vessels

Question 52

Triptans

Answer 52

Sumatriptan (Imitrex), zolmitriptan (Zomig), naratriptan, rizatriptan, eletriptan, almotripan, etc.

Question 53

What are the mechanisms of triptans?

Answer 53

Cause vasoconstriction via stimulation of 5-HT1B serotonin receptors on blood vessel walls, also reduce inflammation of vessels by stimulation of 5-HT1D serotonin receptors in brainstem.

Question 54

Phantom limb pain

Answer 54

-Tingling, itching, burning, aching, stabbing sensations that appear to emanate from body parts post amputation

Question 55

What was the historical theory for phantom limb pain?

Answer 55

Historically, the dominant theory for cause of phantom limb pain was the presence of neuromas that generated nonsense sensations

Question 56

What are todays theory of phantom limb pain?

Answer 56

- maladaptive reorganization of the primary sensory cortex - conflict between signals received from the amputated limb (proprioception) and visual information - vivid limb position memories that emerge after amputation

Question 57

What are common treatments for phantom limb pain?

Answer 57

Common treatments are antidepressants, spinal cord stimulation, vibration therapy, acupuncture, hypnosis, biofeedback, and mirror therapy. Generally not relieved by opiate analgesics.